Oral administration of insulin in solid form to nondiabetic and diabetic dogs

It was previously demonstrated that a biologically active insulin could cross the mucosal membrane in the gut by using surface active substances. In this report we describe studies in which insulin administered orally, in a solid formulation, was effectively absorbed in the canine model. The insulin was mixed with cholate and soybean trypsin inhibitor. It was delivered orally, as enterocoated microtablets, to nondiabetic and diabetic (pancreatectomized) dogs in a fasting state. The time interval between the administration of the drug and the beginning of a decrease in the plasma glucose levels was 60-140 min. This decrease reached a minimum level of 20-40 % of the initial values and lasted for more than 90 min following administration of the drug. In this model a pronounced increment in plasma insulin levels was shown prior to the drop of plasma glucose concentrations. It is concluded that with this novel oral insulin formulation a beneficial biological effect can be achieved in the treatment of diabetes.     

Defect-Property Correlations in Garnet Crystals. *VII: The Electrical Conductivity and Defect Structure of Yttrium Aluminum and Yttrium Iron Garnet Solid Solutions

The conduction mechanisms in yttrium aluminum and yttrium iron garnet solid solutions have been studied as a function of temperature, iron concentration and partial pressure of oxygen. At low concentrations of iron, ac conductivity and ionic transference measurements show the solid solution to be a mixed ionic-electronic conductor with an ionic mobility characterized by an activation energy of 2.6–2.8eV and a p-type electronic conductivity with activation energy of 3.0–3.3eV. High concentrations of iron cause a dramatic increase in the electrical conductivity connected with the formation of an Fe impurity band found to lie 1.9eV below the conduction band. Transport through this band is via an activated hopping process with an activation energy of 0.7eV for 6 fraction percent Fe. A defect model is presented which is consistent with our experimental observations including the conductivity maxima obtained at high PO₂'s for high Fe levels.     

Retrograde transport from the yeast Golgi is mediated by two ARF GAP proteins with overlapping function

ARF proteins, which mediate vesicular transport, have little or no intrinsic GTPase activity. They rely on the actions of GTPase-activating proteins (GAPs) for their function. The in vitro GTPase activity of the Saccharomyces cerevisiae ARF proteins Arf1 and Arf2 is stimulated by the yeast Gcs1 protein, and in vivo genetic interactions between arf and gcs1 mutations implicate Gcs1 in vesicular transport. However, the Gcs1 protein is dispensable, indicating that additional ARF GAP proteins exist. We show that the structurally related protein Glo3, which is also dispensable, also exhibits ARF GAP activity. Genetic and in vitro approaches reveal that Glo3 and Gcs1 have an overlapping essential function at the endoplasmic reticulum (ER)-Golgi stage of vesicular transport. Mutant cells deficient for both ARF GAPs cannot proliferate, undergo a dramatic accumulation of ER and are defective for protein transport between ER and Golgi. The glo3Delta and gcs1Delta single mutations each interact with a sec21 mutation that affects a component of COPI, which mediates vesicular transport within the ER-Golgi shuttle, while increased dosage of the BET1, BOS1 and SEC22 genes encoding members of a v-SNARE family that functions within the ER-Golgi alleviates the effects of a glo3Delta mutation. An in vitro assay indicates that efficient retrieval from the Golgi to the ER requires these two proteins. These findings suggest that Glo3 and Gcs1 ARF GAPs mediate retrograde vesicular transport from the Golgi to the ER.     

Autoamputation of the fingertips in an 11-year-old boy

This study examined the relationship of plasma renin activity (PRA) to the likelihood of maintaining blood pressure control after discontinuation of antihypertensive medication. Patients whose blood pressure was previously treated and controlled in the Hypertension Detection and Follow-up Program were enrolled in the Dietary Intervention Study of Hypertension. After stratification by obesity, patients were randomized to discontinue medication with no dietary intervention, sodium restriction, or weight reduction for the obese. Among 496 subjects in the Dietary Intervention Study of Hypertension, 75 were randomly selected for PRA measurement at 4 months after intervention, and all had their blood pressure under control at that time. Patients were followed up for 56 weeks after randomization. The endpoint was return to antihypertensive medication due to elevated diastolic blood pressure. Kaplan-Meier survival analysis showed that subjects with PRA < or = 53.3 ng/100 mL/h, the median level, had a lower cumulative success rate for remaining off antihypertensive drug than those with PRA above the median (P = .046). In Cox regression analysis controlling for 24-h urinary sodium level, baseline diastolic blood pressure, age, sex, race, obesity, and dietary intervention group, a unit decrease in log PRA was associated with a 2.78-fold increase in risk of returning to drug (P = .006); this inverse relationship was independent of dietary intervention and change in diastolic blood pressure in the first 4 months before PRA was measured. The data indicate that patients with low PRA are less likely to maintain blood pressure control without drugs than patients with high PRA.